The research proposed in this grant application is intended to use the mouse as a representative mammal to: 1. Investigate the genetic control of primary sex determination by analyzing mutations that cause partial or complete sex reversal; 2. Investigate the molecular organization of the Y chromosome, especially those DNA sequences involved in primary sex determination and recombination with the X chromosomes; 3. Expand the mouse linkage map by finding and mapping new loci and more exactly mapping established mutations; 4. Identify and characterize loci involved in male Fl sterility resulting from interbreeding different species of Mus and crossing several species of Mus to laboratory inbred strains. Methodologies include formal genetic, cytogenetic, and biochemical and molecular techniques (i.e., formal genetic linkage crosses; protein, RNA, and DNA preparations; meiotic and mitotic chromosome preparations; G and RBA chromosome banding; DNA hybridization in situ; leucocyte and fibroblast cultures; Southern and Northern blot analysis; DNA library construction; DNA subcloning; and cDNA preparation).